Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase.

Abstract

We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve. To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats. At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2'-deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting. : Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF-alpha mRNA were unchanged in VMH lesioned rats. VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E(2), induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.